Albuterol to Improve Respiratory Strength in SCI

NCT ID: NCT02508311

Last Updated: 2024-05-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-01
• Study Completion Date: 2023-02-28

Brief Summary

Spinal cord injury (SCI), especially involving the cervical and upper thoracic segments, can significantly compromise respiratory muscle function. Respiratory complications can ensue, including lung collapse and pneumonia, which are the primary cause for mortality in association with traumatic SCI both during the acute and chronic phases post-injury. Lesions at the level of the cervical or high thoracic spinal cord result in respiratory muscle weakness, which is associated with ineffective cough, mucus retention, and mucus plugging. Despite the fact that pulmonary complications are a major cause of morbidity and mortality in this population, there is a paucity of effective interventions in the SCI population known to improve respiratory muscle strength with pharmacologic interventions receiving little to no attention. The current objective of this study is to determine the effectiveness of 16 weeks of sustained release oral Albuterol to; (1) improve respiratory muscular strength, and (2) improve cough effectiveness.

Detailed Description

Although the past 40 years has witnessed a substantial improvement in the acute and chronic management of persons with SCI, mortality remains high during the first year post-injury, and pulmonary complications including pneumonia, lung collapse (atelectasis), respiratory failure, and thromboembolism are the predominant cause. The propensity for pulmonary complications among subjects with SCI stems from paralysis of respiratory muscles. Injury to the cervical and upper thoracic cord significantly compromises function of the diaphragm, intercostal muscles, accessory respiratory muscles, and abdominal muscles. Respiratory muscle dysfunction is manifest as diminution in lung volumes, reduction in maximal static inspiratory and expiratory mouth pressures (MIP and MEP, respectively), and reduction in peak cough pressure and flow. Cough effectiveness is contingent upon both inspiratory and expiratory muscle strength; increasing the pressure-generating capacity of the inspiratory and expiratory muscles in persons with tetraplegia and high paraplegia may, therefore, translate to improved cough effectiveness and reduction in the propensity for atelectasis and, possibly, pneumonia.

Respiratory muscle training, often utilizing simple hand-held portable resistive or threshold training devices, appears to have marginal effects on vital capacity and maximal static mouth inspiratory and expiratory pressures (MIP and MEP, respectively), although data is inconclusive. Pharmacologic interventions to improve respiratory muscle strength have received little attention in the SCI population. Studies involving oral beta-2 adrenergic agonists, which have been shown to elicit anabolic effects on skeletal muscle in young men and an increase in muscle strength among patients with facioscapulohumeral muscular dystrophy, have also demonstrated salutary effects in persons with SCI. There are many foreseeable advantages of a pharmacologic approach to improve respiratory muscle strength in persons with SCI. For instance, RMT can be physically demanding and time consuming, compliance can be an issue, and sustainable improvements have not been realized. The intent in the present proposal is to enroll a targeted cohort of 24 comparatively weaker subjects with tetraplegia and high paraplegia in a randomized, double-blind, placebo-controlled, parallel group trial to assess the effects of an oral beta-2 agonist upon respiratory muscle strength and cough effectiveness.

Conditions

Spinal Cord Injury; Respiratory Muscle Weakness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active Oral Beta-2

Subjects will receive 16 weeks of active medication.

Group Type: ACTIVE_COMPARATOR

Oral Albuterol Extended Release

Intervention Type: DRUG

Subjects will receive extended release Albuterol, 4mg twice daily for the first week. The remaining 15 weeks subjects will receive extended release Albuterol, 8mg twice daily.

Placebo

Subjects will receive 16 weeks of placebo medication.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subjects will receive placebo tablets twice daily for 16 weeks.

Interventions

Oral Albuterol Extended Release

Subjects will receive extended release Albuterol, 4mg twice daily for the first week. The remaining 15 weeks subjects will receive extended release Albuterol, 8mg twice daily.

Intervention Type: DRUG

Placebo

Subjects will receive placebo tablets twice daily for 16 weeks.

Intervention Type: DRUG

Other Intervention Names

VoSpire

Eligibility Criteria

Inclusion Criteria

• Male or Female age 18 to 80
• Chronic spinal cord injury ( 1 year since injury)
• Neurological level of injury between C3-C8 (Tetraplegia)
• Neurological level of injury between T1-T6 (High Paraplegia)
• Males with maximal inspiratory pressure (MIP) < 90 cm H2O or
• Females with maximal inspiratory pressure (MIP) < 65 cm H2O

Exclusion Criteria

• Smoking, active or history of smoking with the past year
• Ventilator Dependence
• History of blast injuries to the chest
• Antidepressant use
• History of asthma
• Active respiratory disease or recent(within 3 months) respiratory infections
• Uncontrolled hypertension or cardiovascular disease
• Current use a beta-2 adrenergic agonists
• History of epilepsy or seizure disorder
• Hyperthyroidism
• Currently taking corticosteroids
• Currently taking monoamine oxidase inhibitors or tricyclic antidepressants
• Hypersensitivity to albuterol or any of its' constituents
• Pregnant
• Use or are suspected of using over-the counter supplements or prescribed medications with anabolic characteristics (promotes improvements to muscle mass and strength) including, but not limited to:

• creatine monohydrate
• anabolic steroids (e.g., testosterone)
• growth hormone
• substances with similar actions or indications as those listed

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Greg Schilero, MD

Role: PRINCIPAL_INVESTIGATOR

James J. Peters Veterans Affairs Medical Center

Locations

James J. Peters VA Medical Center, Bronx, NY

The Bronx, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

SCH-15-011

Identifier Type: OTHER

Identifier Source: secondary_id

B1910-P

Identifier Type: -

Identifier Source: org_study_id